1. Field of the Invention
The present invention is broadly directed to a method for inhibiting activation of latent human immunodeficiency virus (HIV). The invention is also directed to a method for inhibiting replication of HIV. The present invention is particularly directed to the use of a particular class of isozyme selective Protein Kinase C (PKC) inhibitors for treating HIV infection.
2. Description of Related Art
The HIV epidemic continues to grow at a rapid rate, and the clinical manifestations associated with this viral infection present increasingly more complex medical and socioeconomic problems. Acute HIV infection leads to a period of rapid viral replication, followed by viremia that results in infection of 1% or more of circulating T lymphocytes, the primary target of the virus. Viremia is transient, however, because the cells infected with HIV are removed from circulation by an effective host immune response that results in a 10-to 100-fold decrease in the HIV-infected T cells. Unfortunately, no effective therapy yet exists for preventing viral activation after exposure. Thus, although the initial host response is effective in reducing and controlling HIV-infected cell numbers, it is not sufficient to prevent the postintegration latent or low-level-persistent (LLP) asymptomatic infections of host reservoir cells, such as circulating CD4+T lymphocytes and monocyte/macrophages. Thus, the ultimate pathogenic effects of HIV are not prevented and after induction from the latent or LLP state, acquired immune deficiency syndrome (AIDS) develops.
No cure has yet been found for HIV infection. Current treatments for HIV infection attempt to retard the progress of the disease or relieve its symptoms. Treatment in use today include certain dideoxynucleotides such as azidothymidine (AZT or zidovudine, Burroughs Wellcome), dideoxyinosine (ddI, Bristol-Myers Squibb) or dideoxycytidine (ddC, Hoffman-LaRoche). These agents can be toxic. Their applicability is limited because of the appearance in some patients of onerous, and sometimes lethal, side effects. These side effects include myelosuppression, peripheral neuropathy, and pancreatitis. In some patients, AZT has lost its effectiveness after prolonged use. While other drugs have been proposed for treatment of HIV infection, including the recent introduction of several HIV protease inhibitors, none have yet been demonstrated to be completely effective. Therefore, there remains a need in the art to develop additional therapeutic agents to treat HIV infection.